Trophic factors play an important role in the
development of neurons and glia. In order to
study the involvement of neurotrophins in
human cortical development, human fetal
parietal cortical tissue, obtained after early
elective abortions, was transplanted to cortical
cavities in immunosuppressed rats. Using in situ
hybridization it was demonstrated that nerve
growth factor, brain-derived neurotrophic factor
and neurotrophin-3 mRNAs are expressed in
developing human cortical xenografts. We conclude
that neurotrophins may play a role in
human cortical development and rat-derived
astroglial cells could be involved in establishing
reciprocal “permissive sites”.

Christian Humpel

Ingrid Strömberg

Lars Olson

Expression of Nerve Growth Factor, Brain-Derived Neurotrophic Factor and Neurotrophin-3 mRNAs in Human Cortical Xenografts

Arg-Gly-Asp peptides (RGD) were synthesized
and chemically coupled to the bulk of N-(2-hydroxypropyl) methacrylamide-based polymer
hydrogels. Fourier Transform Infrared Spectroscopy
(FFIR) and amino acid analysis confirmed
the peptide coupling to the polymer. Activated
and control (unmodified) polymer matrices were
stereotaxically implanted in the striata of rat
brains, and two months later the brains were
processed for immunohistochemistry using antibodies
for glial acidic fibrillary protein (GFAP),
laminin and neurofilaments. RGD-containing
polymer matrices promoted stronger adhesion to
the host tissue than the unmodified polymer
matrices. In addition, the RGD-grafted polymer
implants promoted and supported the growth
and spread of GFAP-positive glial tissue onto
and into the hydrogels. Neurofilament-positive
fibers were also seen running along the surface
of the polymer and, in some instances, penetrating
the matrix. These findings are discussed
in the context of using bioactive polymers as a
new approach for promoting tissue repair and
axonal regeneration of damaged structures of
the central nervous system.

S. Woerly

G. Laroche

R. Marchand

J. Pato

V. Subr

K. Ulbrich

Intracerebral Implantation of Hydrogel-Coupled Adhesion Peptides: Tissue Reaction

One of the limitations of many bridging
experiments in neural transplantation is that the
CNS tissues cannot be sutured. Fibrin glue is a
two-component system derived from whole
blood which, when mixed, reproduces the final
stage of blood coagulation and solidifies. Many
experimental studies of humans and animals
show that fibrin glue repair of peripheral nerves
is almost equivalent to microsurgical sutures. In
this study, we attempted to extend its use to
CNS tissues and transplants. Two techniques
were tried: (1) Bilateral parietal knife cuts were
performed by stereotaxic technique in six rats.
Fibrin glue was applied in the right-side cortical
lesion. Immunohistochemistry using antisera to
tyrosine hydroxylase (TH), glial fibrillary acidic
protein (GFAP), laminin and neurofilament
(NF) was essentially similar between the control
and treatment groups. The immunoreactivity of
each marker revealed no significant differences
between the two groups on days 1, 7 and 30.
There was no difference in terms of gliosis or
microvascular proliferation. (2) Embryonic day
16 fetal locus coeruleus was grafted together
with E16 cortex to the anterior chamber of sympathectomized
eyes. In the six eyes of the glue
treatment group, the parietal cortical piece and
the locus coeruleus piece were joined together
before grafting by immersing them in the
solution of fibrin glue. In the eight eyes of the
control group, pieces of parietal cortex and locus
coeruleus were introduced individually and approximated
by gently pressing the cornea. The
sizes of double grafts showed no significant
difference between groups during six weeks
postgrafting. The immunohistochemical pictures
using antisera against TH, GFAP and laminin
were similar in both groups. Catecholaminergic
fibers from the grafted locus coeruleus were
found bridging over into the parietal cortical
piece in both the control and treatment groups.
There was no significant difference in TH-positive
nerve fiber density between tissue glue joined
and control double intraocular grafts. In
conclusion, fibrin glue can be used as an adhesive
agent in CNS tissues without hampering
the outgrowth of neurites or causing adverse
tissue reactions in fetal or adult nervous tissues.

Henrich Cheng

Susanne Almström

Fibrin Glue Used as an Adhesive Agent in CNS Tissues

Enteric neurons and glia cells were isolated
from adult Sprague Dawley rats. A procedure is
described using a combination of microdissection
and mechanical dissociation after
enzyme treatment which yields large numbers of
cell clusters suitable for tissue culture and
grafting into the injured spinal cord. Differentiated
enteric ganglia remained viable for at
least 5 days in vitro Cultured neurons expressed
histochemical reactivity for acetylcholinesterase
and nicotinamide adenine dinucleotide phosphate
diaphorase. Nestin positive glia, which
represented a population of non-myelinating
enteric Schwann cells, could also be identified in
cultures maintained 5 days or longer in vitro.
The myenteric plexus of adult rats can provide a
readily available source of neurons and
Schwann cells for grafting to the central nervous
system.

Christine B. Jaeger

Isolation of Enteric Ganglia from the Myenteric Plexus of Adult Rats

The long-term fate of multiple intrahippocampal
allogeneic transplants of fetal basal
forebrain tissue was studied in neonatally
tolerised and immunised groups of rats with
lesions of the fimbria-fornix. Despite the good
survival of the allografts in all groups,
unexpected transplant-associated host hippo-campal
neuropathology was discovered 12
months after transplantation, which consisted of
(i) CA1 cell degeneration and (ii) abnormal
accumulations of phosphorylated neurofilaments
in neuronal perikarya and axonal swellings only
within the host hippocampal neuropil and not of
the transplanted tissue. This neurofilament
abnormality, identified by RT97 immunohistochemistry,
was significantly greater in the
transplanted rats compared to the non-grafted
lesion-only and sham-lesioned rats <mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:mtext>p&lt;0</mml:mtext><mml:mn>.01</mml:mn></mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mrow></mml:math>
. The
same type of neurofilament abnormality was
again observed in a second, separate experiment
using unilateral and bilateral syngeneic and
allogeneic transplants. The neuropathology was
significantly <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mrow><mml:mo>(</mml:mo><mml:mrow><mml:mtext>p&lt;0</mml:mtext><mml:mn>.05</mml:mn></mml:mrow><mml:mo>)</mml:mo></mml:mrow></mml:mrow></mml:math>
 greater in the transplanted
side of the unilateral transplanted rats
compared to the non-transplanted lesion-only
control side of the same animals, showing that
transplantation per se was a major factor
involved in the pathogenesis of this neuropathology,
irrespective of the type of transplant
(syngeneic or allogeneic). In addition, a small
degree of neurofilament abnormality was also
found within the transplants in the second
experiment, but not in the first. The results show
that, under certain conditions, specific local
neuropathological damage to the surrounding
host neural tissue can develop in long-surviving
allografted and syngrafted animals.

Sanjay N. Patel

Tim R. Kershaw

John Williams

Jeffrey A. Gray

Peter L. Lantos

John D. Sinden

Neuropathological Sequelae of Long-Term Allogeneic and Syngeneic Neural Transplantation into the Hippocampus

Past studies have experienced difficulty in
achieving graft survival and behavioural
recovery after sensorimotor cortex lesions. In the
present work, adult female rats trained
preoperatively to cross a narrow beam for food
reward were maintained in standard group
cages or an enriched environment, commencing
one week after a unilateral lesion. One month
post-lesion, half of these rats received multiple
suspension grafts of (E20) fetal frontal cortex,
placed adjacent to the lesion cavity, and 8 days
later recovery of beam-walking skills was
examined for a six-week period. The grafts
survived in all cases with an appropriate lesion,
a notable result given the one month lesion-graft
delay, but graft volume was not influenced by
postoperative environment. The substantial
lesion-induced deficits evident just prior to
differential housing showed a marked reduction
by the start of post-graft testing, but relative to
intact controls a persistent deficit in foot slip
errors occurred in all lesion groups. Irrespective
of graft status, postoperative enrichment
prevented the occurrence of severe foot slips,
especially early in retraining. The frontal grafts,
however, enhanced beam-walking recovery by
reducing the overall frequency of foot slips on
early post-grafting sessions, an effect we suggest
is related to graft-derived trophic influences, but
this measure was not significantly improved by
postoperative enrichment.

Michael A. Christie

John C. Dalrymple-Alford

Behavioural Consequences of Frontal Cortex Grafts and Enriched Environments after Sensorimotor Cortex Lesions

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Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

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Chief Editor, Professor Baudry, is currently University Professor at Western University of Health Sciences in Pomona, CA. His research focuses on understanding the molecular/cellular mechanisms of learning and memory and neurodegeneration.

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Neural Plasticity - Table of contents 1995

title

Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

Neural Plasticity